Study of Isavuconazole Prophylaxis in Adults With Acute Myeloid Leukemia/Myelodysplastic Syndrome (AML/MDS) and Neutropenia

Study Drug Administration:

If participant is found to be eligible to take part in this study, participant will take
isavuconazole by mouth every 8 hours for the first 6 doses (48 hours) and then 1 time each
day after that.

The capsules should be swallowed whole. Do not chew, crush, dissolve, or open the capsules.

If at the start of the study participant is unable to take participant's dose by mouth,
participant will receive the study drug by vein over about 1 hour every 8 hours for the first
6 doses and then 1 time each day after that for up to 4 days.

If there is a brief period where participant is unable to take the dose by mouth, participant
will receive isavuconazole by vein over about 1 hour. Participant will switch back to taking
the dose by mouth again as soon as participant is able to do so.

Participant will be given a study drug diary to keep track of each dose of study drug that
participant has taken, the time the dose was taken, and any missed or vomited doses.
Participant should bring the study drug diary with participant to every visit.

Length of Study:

Participant may continue to take the study drug for up to 12 weeks. Participant will no
longer be able to take the study drug if the disease gets worse, if participant has a
complete remission of the disease (if the disease goes away), if a breakthrough fungal
infection occurs, if intolerable side effects occur, or if participant is unable to follow
study directions.

Participation in the study will be over after the End-of-Study Visit.

Study Visits:

Every week:

- Blood (about 2-3 teaspoons) will be drawn for routine tests 1-2 times each week.

- Blood (about 2-3 teaspoons each time) will be drawn twice a week to check for a fungal
infection.

During Weeks 1, 4, 7, and 10, participant will have a physical exam.

On Days 8 and 15, blood (about 1 teaspoon) will be drawn for pharmacokinetic (PK) testing. PK
testing measures the amount of study drug in the body at different time points.

On Day 10, participant will have an EKG.

During Week 2 and then every other week after that (Weeks 4, 6, 8, and so on), blood (about 1
teaspoon) will be drawn to measure the iron stores in participant's body.

If at any time the doctors think it is needed:

- Participant will have a chest x-ray or CT scan to check for fungal infections in
participant's lungs.

- Blood (about 2-3 teaspoons) will be drawn to check for fungal infections.

- If participant has a bone marrow test done to check the status of the leukemia as part
of participant's standard of care, it will be checked for iron content.

End of Study:

About 30 days after the last dose of the study drug:

- Participant will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

Inclusion Criteria:

1. Patients with either newly diagnosed AML or MDS who have either begun (within 4 days
of starting study drug) or are planned to begin specific treatment for their AML/MDS.
Patients who are participating in other therapeutic clinical trials for their AML/MDS
may participate in this trial.

2. Patients must have or be anticipated to have neutropenia (absolute neutrophil count
(ANC) <0.5 x 109/L) (75) for >/= 7 days as a result of treatment of their AML/MDS.

3. Age >/= 18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

5. Patients must have reasonable liver function, i.e., total bilirubin AST/ALT
6. Patients must be able to take oral medications, although a brief period of IV therapy
(<4 days) is permitted at trial entry.

7. Patients must be willing and able to provide written informed consent for the trial.

8. Women of childbearing potential (WOCBP) must practice 2 effective methods of birth
control during the course of the study. Male patients who are partners of WOCBP should
also practice an effective method of contraception. Effective methods of birth control
include diaphragm or condoms with spermicidal foam or jelly, birth control pills
(BCPs), injections or patches, intra-uterine devices (IUDs) and surgical
sterilization.

9. Postmenopausal women must be amenorrheic for =/>12 months to be considered of
non-childbearing potential.

10. Women and men must continue birth control for the duration of the trial and =/>3
months after the last dose of study drug.

11. All WOCBP MUST have a negative pregnancy test prior to first receiving study
medication.

Exclusion Criteria:

1. Proven, probable or possible IFI within the previous 30 days.

2. Use of any systemic antifungal therapy for > 72 hours during the week prior to study
drug initiation..

3. History of hypersensitivity or idiosyncratic reactions to azoles.

4. Patients with familial short QT syndrome or with QTc interval
5. Patients on strong CYP3A4 inducers or inhibitors that cannot be discontinued.

6. Women who are pregnant or nursing, or intend to be/do so during the course of the
study.

7. Patients with severe hepatic impairment (Child-Pugh class C).

8. Patients with known or suspected Gilbert's syndrome at the time of study enrollment.

9. Patients with known gastrointestinal conditions that could potentially interfere with
absorption of orally administered medications.

10. Any condition that, in the opinion of the investigator, may interfere with the
objectives of the study, e.g., any condition requiring the use of prohibited drugs or
unstable medical conditions other than AML/MDS, such as a cardiac or neurologic
disorder expected to be unstable or progressive during the course of the study (e.g.,
seizures or demyelinating syndromes, acute myocardial infarction within 3 months of
study entry, myocardial ischemia or unstable congestive heart failure, unstable
arrhythmias).